In laboratory and clinical settings, it is often necessary to take, contain, transport, and store biological samples, such as blood or blood products, to determine the concentration of various components in the sample. The analysis of biological fluids to confirm the levels or concentrations of various components contained therein is an accepted clinical practice for the determination of the pharmacokinetic properties of drug compounds in the bloodstream.
Conventional liquid sample collection, handling, transport, and storage, in a glass or plastic tube, has many problems associated with it, including: (1) the risk of container breakage or leakage which causes loss of sample and the danger of infection to the handlers; (2) sample instability during shipment and storage; (3) refusal of transport carriers to accept liquid biohazardous shipments, (4) requiring the collection of more sample than is necessary for testing, to ensure quantities compatible with common laboratory methods of serum or plasma preparation and subsequent analysis, and (5) the fact that limited quantities of fluid available for extraction from small animals such as mice and rats do not allow enough serial liquid samples to be collected from each animal.
In the case of certain blood component determinations, the handling of the blood samples can also be a critical part of the ultimate accuracy of measurement in the sample. Therefore, even when a blood sample is removed from the body, the concentration of the component within a liquid blood sample can change over time.
To overcome these problems, in one approach, a biological sample, e.g., a drop or two of whole blood is collected on collection media such as specially manufactured paper and dried prior to transport. These dried blood spot (DBS) samples can be obtained using small amount of blood (typically 15 μL-20 μL), can be mailed and are accepted by all common carriers. Dried blood spots have the advantage of helping to preserve certain components for later analysis.
The extraction of blood and deposition of blood spots from test subjects onto suitable media such as a collection media is generally labor intensive and requires skill to accurately pipette and dispense blood onto paper without causing separation of blood components as the blood disperses on the paper. Inconsistent deposition of blood can produce variation in subsequent analysis of DBS samples.
Further, manual dispensing of spots onto cards may not accurately position the sample. The variation from manual positioning creates difficulties for subsequent automation used to punch blood spots from cards or analyze the spots directly, as it requires specialized instrumentation that must first identify the location of the blood spot before processing. This requirement introduces considerable complexity to the instrumentation and introduces reliability issues to the proper analysis of misplaced blood spots.
Typically, pre-clinical pharmacokinetic studies require from eight (8) to twelve (12) serial blood samples taken at specified time points during a 24 hour period. For each time point, one (1) to four (4) dried blood spots are collected. Commercially available dried blood spot cards for bioanalytical analysis hold up to 4 dried blood spots each. One (1) card is used for each time point. After collection of the blood onto the card the blood must be allowed to dry for a minimum of two (2) hours. Space must be available for air circulation around the card to allow each liquid sample to dry. When large numbers of test subjects are being sampled, the large number of blood spot cards generated requires significant physical space to separate cards for drying the blood spots. Each individual card must be labeled for subject identification and identification of the time point for that subject.